Soluplus® nanomicelles enhance IgG neutralizing properties against Shiga toxin type 2

Shiga toxin (Stx) is the main virulence factor of Stx-producing Escherichia coli, a pathogen responsible for developing Hemolytic Uremic Syndrome. Nowadays, no specific treatment exists for this disease, and nanomicelles may be an excellent platform for the delivery of specific compounds, including immunoglobulins (IgG), for therapeutic or diagnostic strategies. In this work, Soluplus® nanomicelles (NM) were associated with IgG against Stx type 2 (NM-IgG-Stx2). Physicochemical evaluation of NM-IgG-Stx2 was performed by Dynamic Light Scattering, Uv–Vis, Fluorescence, and Circular Dichroism spectroscopy.

Highlights

• Soluplus® nanomicelles associate with IgG in a surface absorption model (NM-IgG-Stx2).
• IgG preserves structural conformation and functionality after Soluplus® interaction.
• Soluplus® nanomicelles potentiate Stx2 neutralization properties of IgG.
• NM-IgG-Stx2 improves neutralization properties against purified and native Stx2.

Morphology was analyzed by transmission electron microscopy. An in silico analysis of NM-IgG-Stx2 association was performed, and neutralization properties against purified Stx2 and Stx-derived supernatants were analyzed on Vero and HGEC cells. Our results suggest that IgG-Stx2 assemble with NM, and the interaction improves the Stx2 neutralization capacity of the antibody. These results suggest that NM may enhance IgG-Stx2 paratope availability and may be an excellent platform for the recognition and neutralization of Stx2.

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Materials

Soluplus®, a grafted polymer of polyvinyl caprolactam, polyvinylalcohol, and polyethyleneglycol (PVCL-PVA-PEG), was a kind gift from BASF (Buenos Aires, CABA, Argentina). Minimum Essential Medium (MEM), Medium 199, l-Glutamine 200 mM, trypsin and Ethylenediaminetetraacetic acid (EDTA) 10x, phosphate buffer saline (PBS), and penicillin/streptomycin 100 U/ml were purchased from Gibco (Grand Island, NY, USA). Stx2a was acquired from Phoenix Laboratory (Tufts Medical Center, Boston, USA).

Daniel Girón, Gabriela E. Gómez, Juan J. Casal, José M. Delfino, Fernando Gomez, Cristina Ibarra, María M. Amaral, Diego A. Chiappetta, Marcela A. Moretton, Flavia Sacerdoti, Soluplus® nanomicelles enhance IgG neutralizing properties against Shiga toxin type 2, Journal of Drug Delivery Science and Technology, 2024, 105606, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.105606.

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